Inflammation-Associated Lipid Mediators in Cholestatic Hepatobiliary Diseases and Effect of PAF-AH

胆汁淤积性肝胆疾病中炎症相关脂质介质及 PAF-AH 的作用

• 批准号: 12670456
• 负责人: SHODA Junichi
• 金额: $ 2.56万
• 依托单位: THE UNIVERSITY OF TSUKUBA
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670456/
• 关键词: bilirubin; obstractive cholestasis; primary hepatolithiasis; hepatobiliary malignancy; biliary secretory mechanism; canalicular membrane transporter; bile acid; oxidative stress; 経皮経肝胆道ドレナージ; 輸送蛋白; 胆汁うっ滞; 脂質メディエーター; 炎症病態; ホスホリパーゼAz; 血小板活性化因子

The transport of biliary constituents across the canalicular membrane is the rate-limiting step in bile formation. Since long-standing biliary obstruction and complication of cholangitis associated with biliary infection have a large influence upon the hepatic secretory function through inflammation-related oxidative stress on the liver, interest should be focused on the expression levels of canalicular membrane transporter proteins in the cholestatic liver of patients with hepatobiliary diseases. We determined the molecular and immunohistochemical expression of canalicular transporter proteins, for bilirubin conjugate and bile acid,in the liver of patients with hepatolithiasis and in those of the patients with obstructive cholestasis who had undergone preoperative biliary drainage. Furthermore, their expression levels were correlated with the impairment of biliary secretion.This study concludes that in the liver of hepatobiliary diseases, the altered expression of the canalicular transporters may be associated with the impairment of bile formation and secretion, propably through inflammation-related oxidative stress on the liver.

胆汁成分穿过胆管膜的运输是胆汁形成的限速步骤。由于长期胆道梗阻和胆道感染相关的胆管炎并发症通过肝脏炎症相关的氧化应激对肝分泌功能产生很大影响，因此应关注胆汁淤积性肝脏中胆管膜转运蛋白的表达水平肝胆疾病患者。我们测定了肝内胆管结石患者和术前接受胆道引流的梗阻性胆汁淤积患者肝脏中胆红素结合物和胆汁酸的小管转运蛋白的分子和免疫组织化学表达。此外，它们的表达水平与胆汁分泌受损相关。这项研究的结论是，在肝胆疾病的肝脏中，小管转运蛋白的表达改变可能与胆汁形成和分泌受损有关，可能是通过炎症相关的氧化对肝脏的压力。

项目成果

Asano, T., Shoda, J., et al.: "Expression of cyclooxygenase-2 in carcinoma of the gallbladder-crucial role of arachidonate metabolism in tumor growth and progression"Clin Cancer Res. 8. 1157-1167 (2002)

Asano, T., Shoda, J.等人：“胆囊癌中环氧合酶-2的表达——花生四烯酸代谢在肿瘤生长和进展中的关键作用”Clin Cancer Res。

Shoda, J., et al.: "Etiological significance of metabolic defects of cholesterol, phospholipid, and bile acid in the liver of patients with intrahepatic calculi"Hepatology. 33. 1194-1205 (2001)

Shoda, J. 等人：“肝内结石患者肝脏中胆固醇、磷脂和胆汁酸代谢缺陷的病因学意义”肝病学。

Shoda, J., Oda, K., Suzuki, H., Sugiyama, Y., Ito., K, Cohen, D.E., Feng, L., Kamiya, Nimura, Y., Miyazaki, H., Kano, M., Matsuzaki, Y., Tanaka, N.: "Metabolic defects of cholesterol, phospholipid, and bile acid in the liver of patients with intrahepatic

Shoda, J.、Oda, K.、Suzuki, H.、Sugiyama, Y.、Ito., K、Cohen, D.E.、Feng, L.、Kamiya, Nimura, Y.、Miyazaki, H.、Kano, M.

Asano, T., Shoda, J., et al.: "Expression of cyclooxygenase-2 in carcinoma of the gallbladder-crucial role of arachidonate metabolism in tumor growth and progression"Clin Cancer Res. 8. 1157-1167 (2002)

Asano, T., Shoda, J.等人：“胆囊癌中环氧合酶-2的表达——花生四烯酸代谢在肿瘤生长和进展中的关键作用”Clin Cancer Res。

Shoda,J. et al.: "Metabolic defects of cholesterol, phospholipid, and bile acid in the liver of patients with intrahepatic calculi, and etiological significance"Hepatology. (In press). (2001)

绍达，J.